INTRODUCTION — Testicular germ cell tumors (GCTs) can consist of one histologic pattern or represent a mix of multiple histologic types. Testicular GCTs are divided into two groups: pure seminoma and nonseminomatous GCTs (NSGCTs) [1,2]. Patients with stage I seminoma have an excellent prognosis following radical inguinal orchiectomy. Therefore, treatment can be tailored to individual patient preferences.
The treatment approach for patients with stage I seminoma is reviewed here. An overview of the management of testicular GCTs, the epidemiology, clinical manifestations, diagnosis, and staging of testicular GCTs, and the approach to patients with stage II and stage III seminoma are presented separately.
●(See "Clinical manifestations, diagnosis, and staging of testicular germ cell tumors".)
●(See "Overview of the treatment of testicular germ cell tumors".)
●(See "Treatment of stage II seminoma".)
●(See "Initial risk-stratified treatment for advanced testicular germ cell tumors".)
DIAGNOSIS AND INITIAL TREATMENT — The diagnosis of a testicular malignancy is generally established at radical orchiectomy, which also serves as the initial treatment. For patients with stage I seminoma, this procedure is the definitive management and is generally followed by surveillance (algorithm 1). (See 'Postsurgical management' below.)
Classification as stage I seminoma requires:
●Histologic diagnosis of pure seminoma (without any evidence of nonseminomatous elements) on final pathologic analysis of the orchiectomy specimen.
●No pretreatment elevation of alpha-fetoprotein (AFP).
●No evidence of lymph node involvement or distant metastases based on staging computed tomography (CT) of the abdomen and pelvis, and chest imaging (radiograph or CT). Patients with evidence of more advanced disease on imaging are classified as having stage II seminoma or advanced germ cell tumor. (See "Treatment of stage II seminoma" and "Initial risk-stratified treatment for advanced testicular germ cell tumors".)
●Normal tumor marker studies following orchiectomy. However, patients with stage IS seminoma (ie, those with residual elevation of serum beta-human chorionic gonadotropin [beta-hCG]) after orchiectomy require additional investigation by repeating the elevated tumor marker and obtaining a contrast-enhanced CT of the chest, abdomen, and pelvis to evaluate for disease. However, unlike patients with nonseminomas, these patients are not all necessarily treated as having advanced disease. Patients with progressively rising beta-hCG levels, even in the absence of radiographic disease, may be evaluated for systemic therapy according to their risk-stratification, whereas those with stable, minimally elevated beta-hCG levels may be observed. (See "Initial risk-stratified treatment for advanced testicular germ cell tumors".)
Patients with seminoma do not require surgical staging of the retroperitoneal nodes. Hence, they are classified as "clinical" stage I seminoma using American Joint Committee on Cancer (AJCC) terminology (table 1A-B). Patients with findings of lymphadenopathy by imaging (based on the AJCC staging for clinical regional lymph nodes), and patients who undergo a retroperitoneal node dissection for clinical stage I seminoma and are diagnosed with pathologically involved nodes do not have stage I seminoma; instead, they have more advanced disease and are treated accordingly. (See "Treatment of stage II seminoma" and "Initial risk-stratified treatment for advanced testicular germ cell tumors".)
POSTSURGICAL MANAGEMENT — Approximately 85 percent of patients with stage I seminoma are cured with orchiectomy. Given the likelihood of cure following orchiectomy, we concur with guidelines from the National Comprehensive Cancer Network (NCCN) and recommend surveillance rather than adjuvant therapy [3]. (See 'Surveillance' below.)
For patients who are not willing and able to undergo all the follow-up testing that is involved with surveillance, and for those patients who desire a more aggressive treatment course in order to reduce their risk of relapse, reasonable alternative options to surveillance include:
●Adjuvant single-agent carboplatin (see 'Adjuvant chemotherapy' below)
●Adjuvant radiation therapy (RT) (see 'Adjuvant radiation therapy' below)
Surveillance — We prefer surveillance for patients who are willing and able to adhere to the follow-up schedule. Surveillance achieves the same long-term cure rate as adjuvant therapy and allows most patients to avoid the side effects and late toxicity of chemotherapy and RT. For those patients who relapse during surveillance, treatment is curative for almost all of them. Survival with surveillance is as excellent as that following adjuvant chemotherapy or RT. However, surveillance has not been directly compared with these treatment approaches in a randomized clinical trial [1,4].
For patients undergoing surveillance, we obtain serial radiologic imaging of the abdomen and pelvis with either CT or magnetic resonance imaging (MRI) to ensure early detection of any recurrence. Surveillance with serum tumor markers is optional. (See 'Imaging studies' below and 'Tumor markers' below.)
The main benefit of surveillance is to avoid unnecessary treatment and the associated treatment-related adverse effects among the patients who will not relapse following orchiectomy [1]. Patients contemplating surveillance should be informed that their chance of survival with this approach is excellent with or without the administration of adjuvant therapy, and risk of death is approximately 1 percent or less. Although studies have not shown a clear impact of nonadherence with surveillance on survival outcomes, patients should be advised to strictly adhere to the surveillance schedule. Patients whose relapses are detected early would have more treatment options, including those with less long-term toxicity [5,6].
The effectiveness of surveillance has been consistently demonstrated in different studies [1,7-10]. As examples:
●In one study, the following outcomes were reported in a cohort of 1954 males with stage I seminoma undergoing surveillance who were followed for a median of 15 years [8]:
•For the 369 patients who relapsed (19 percent), the median time to relapse was 14 months. Over 70 percent relapsed during the first two years, and only 7 percent relapsed after year 5.
•In almost all patients, relapsed disease was associated with a good prognosis. The disease-specific survival at 15 years was 99.3 percent.
●In another study that included 1344 males with stage I seminoma managed with surveillance, 173 (13 percent) relapsed at a median of 14 months, but only eight (<1 percent of entire cohort) relapsed beyond three years [9]. Only two of the relapses (1 percent) were intermediate risk at relapse. There were no deaths from disease and only one treatment-related death.
In a partially overlapping database study of 766 patients managed with surveillance, the incidence of late relapse (defined as more than two years after orchiectomy) was 4 percent [10]. In this subset, the pattern of relapse and the subsequent favorable response to treatment were similar to that for early relapse.
Imaging studies — A number of different surveillance imaging recommendations are used for patients with clinical stage I seminoma. Our practice has been consistent with NCCN guidelines [3]. We perform either contrast-enhanced CT or MRI of the abdomen and pelvis at four to six months after orchiectomy and then at 12 months and 18 months. During year 3, we obtain imaging every 6 to 12 months, and every 12 to 24 months in years 4 and 5.
MRI is a reasonable alternative to CT imaging for those who wish to avoid radiation exposure or intravenous CT contrast. For most patients, we prefer to use the same imaging modality (eg, either CT or MRI) throughout surveillance to facilitate comparison with prior scans. However, some patients may choose to initiate surveillance with CT imaging and subsequently switch to MRI to reduce radiation exposure. Chest radiograph is performed as clinically indicated, with chest CT considered in symptomatic patients.
In a phase III trial (TE24 Trial of Imaging and Schedule in Seminomas Testis [TRISST]) of patients with stage I seminoma, surveillance with MRI was noninferior to CT in detecting relapsed disease, suggesting that MRI is a reasonable alternative to CT in this setting [11]. This study also compared less frequent imaging (three imaging studies over three years) with more frequent imaging (seven imaging studies over five years). We do not use the less frequent imaging schedule because it was associated with a higher incidence of stage IIC or greater disease at relapse (absolute increase of 2.5 percent) in this study. Nevertheless, survival outcomes were excellent for all patients diagnosed with and treated for relapsed disease.
In this 2x2 randomized controlled trial, 669 male patients with stage I seminoma who received no postorchiectomy adjuvant therapy were randomly assigned to one of four surveillance plans using either CT imaging (with either three studies over 36 months or seven studies over 60 months) or MRI (using the same two schedules) [11]. At a median follow-up of six years, the relapse rate was 12 percent (82 patients), with a majority occurring within three years of initiating surveillance (all but five patients). The six-year incidence of more advanced (≥stage IIC) relapsed disease was 1.5 percent (10 patients). Fewer patients on MRI surveillance (two patients; 0.6 percent) had advanced disease at relapse compared with those on CT surveillance (eight patients; 2.6 percent); this trend toward MRI superiority met the prespecified criteria for noninferiority.
Additionally, there were fewer relapses with advanced disease while using more frequent surveillance imaging with seven studies (one patient, 0.3 percent) compared with less frequent imaging with three studies (nine patients, 2.8 percent). Among those with relapsed disease who received salvage therapy, 76 of 82 patients (93 percent) were alive and without evidence of disease recurrence, and the overall survival (OS) rate was 99 percent.
Tumor markers — Surveillance with serum tumor markers is optional. Some experts do not follow serum tumor markers for stage I seminoma because they are rarely increased in the absence of radiologic evidence of disease [12,13]. Other experts follow serum tumor markers because they are easy to obtain and can detect relapsed disease alone in a minority of patients. (See "Serum tumor markers in testicular germ cell tumors" and "Active surveillance following orchiectomy for stage I testicular germ cell tumors", section on 'Active surveillance protocols'.)
The clinical utility of serum tumor markers was evaluated in one observational study of 527 males with stage I seminoma managed by surveillance [12]. At a median of 72 months, relapse occurred in 75 males (14 percent). Only 11 of these males (15 percent) had an elevated marker at the time of relapse. Elevated tumor markers (before the documentation of clinical or radiologic progression) were detected in only one male patient (1.3 percent).
Although most relapses for stage I seminoma are diagnosed on imaging, serum tumor markers alone can still detect relapses. In a randomized phase III trial (TRISST) evaluating various surveillance strategies for stage I seminoma, relapsed disease was seen in 82 patients. Among this group, serum tumor markers alone detected first relapses more commonly among patients who were imaged less frequently (5 of 46 patients; 11 percent) than those imaged more frequently (3 of 36 patients; 8 percent) [11].
Patients who are not candidates for surveillance — Some patients may not be candidates for surveillance, either because they decline surveillance in favor of more aggressive therapy or are unable to adhere to surveillance schedules. Patients who decline surveillance and choose to undergo adjuvant treatment should be informed that adjuvant therapy reduces their risk of recurrence, but it does not improve OS. OS is also excellent with surveillance alone following orchiectomy. (See 'Surveillance' above.)
For patients who are still willing to accept the risks of treatment without an OS advantage, adjuvant treatment options include single-agent carboplatin or RT. (See 'Adjuvant chemotherapy' below and 'Adjuvant radiation therapy' below.)
Semen cryopreservation should be offered to all patients diagnosed with testicular cancer prior to instituting postorchiectomy therapy if they wish to preserve fertility. (See "Clinical manifestations, diagnosis, and staging of testicular germ cell tumors", section on 'Cryopreservation of sperm'.)
Adjuvant chemotherapy — For patients who decline surveillance, want to minimize the risk of relapse, and understand the risks of adverse late effects, we suggest single-agent carboplatin over RT. In a randomized trial, relapse-free rates were similar for single-agent carboplatin and adjuvant RT. While there are limited data on the long-term toxicities of carboplatin, adjuvant RT is associated with an increased risk of late toxicities, including death from second malignancies. (See 'Adjuvant radiation therapy' below.)
For patients who select adjuvant carboplatin, some UpToDate contributors offer two cycles rather than one cycle which is associated with reduced risk of relapse. However, other contributors prefer one cycle of carboplatin since OS outcomes are similar to two cycles of carboplatin, and the long-term toxicities of carboplatin are unknown.
Single-agent carboplatin has been investigated in clinical trials as an adjuvant post-orchiectomy option for patients with stage I seminoma. Single-agent carboplatin, rather than a cisplatin-based combination, has been used because it is effective and less toxic.
Adjuvant carboplatin was evaluated in a phase III trial conducted by the European Organisation for Research and Treatment of Cancer (EORTC) [14,15]. In this trial, 1477 males with stage I seminoma were randomly assigned to adjuvant RT or a single course of carboplatin (dosed at an area under the concentration x time curve [AUC] of 7). At a median follow-up of 6.5 years, relapse-free rates were similar with carboplatin and RT (94.7 and 96.0 percent, respectively) [15]. Carboplatin also reduced the rates of a subsequent contralateral germ cell tumor compared with adjuvant RT (2 versus 15 relapses, HR 0.22, 95% CI, 0.05 to 0.95). There were no deaths due to seminoma in the carboplatin arm and one death due to seminoma in the RT arm.
Retrospective analyses have looked at the relapse rate with either one or two cycles of carboplatin [16-22]. In these studies, the relapse rate is consistently higher among patients who received one cycle of carboplatin (approximately 3 to 9 percent) compared with those who received two cycles (0 to 3 percent). However, OS is similar for both treatments.
The prognosis for those patients who do relapse following adjuvant carboplatin is excellent and is similar to that for patients who present with higher stage disease. In a retrospective series of 185 males from 31 centers who were treated for relapsed stage I seminoma following one or two cycles of adjuvant carboplatin, the five-year disease-free survival and OS rates were 82 and 98 percent, respect [23].
The most common acute side effects of carboplatin are thrombocytopenia, and nausea and vomiting. The incidence of late treatment-related toxicities with single-agent carboplatin are unknown. Further details on the treatment-related toxicity in testicular cancer are discussed separately. (See "Treatment-related toxicity in men with testicular germ cell tumors" and "Approach to the care of long-term testicular cancer survivors", section on 'Side effects of treatment'.)
Adjuvant radiation therapy — Adjuvant RT is an appropriate alternative for patients who do not adhere to surveillance and who decline chemotherapy. Adjuvant RT prevents relapse in approximately 96 percent or more of patients with clinical stage I seminoma [7,24]. Although adjuvant RT is associated with an increased risk of long-term toxicities (including an increased risk for death due to second malignancies) this risk has decreased over time, presumably due to reductions in contemporary treatment fields and the doses delivered [25].
The favorable outcome in patients with clinical stage I seminoma who received adjuvant RT is illustrated by a combined analysis of 1893 patients treated between 1989 and 2001 in one of three randomized phase III trials [24]. Although relapses were seen in 4 percent of patients, there were only four deaths from seminoma, and the remaining patients were successfully treated with chemotherapy at the time of recurrence.
The acute side effects associated with RT include fatigue, gastrointestinal effects, myelosuppression, which is usually mild, skin tanning in the treatment area, and impaired fertility, which is generally not an issue with contemporary RT techniques. Late treatment-related toxicities are discussed separately. (See "Treatment-related toxicity in men with testicular germ cell tumors".)
Technique — In patients with clinical stage I seminoma who choose adjuvant paraaortic RT, patients should undergo simulation in the supine position [26]. A clamshell shield should be used to protect the remaining testis to reduce the dose of RT it is exposed to. Tattoos should be placed at the level of the isocenter anteriorly and laterally.
Treatment field — The use of a "hockey stick" or "dog leg" field, which includes the bilateral paraaortic nodes and pelvic lymph nodes, is associated with an excellent cure rate (image 1) [27,28]. This approach includes all of the regional lymph nodes of the involved testicle that are at risk for micrometastatic disease [29]. RT to the inguinal orchiectomy scar and ipsilateral scrotal contents is probably unnecessary, even if scrotal violation occurred during surgery.
Because the paraaortic lymph nodes are the initial nodal group to be involved in the majority of patients who experience tumor spread, paraaortic strip RT protocols were introduced in an effort to decrease treatment-related morbidity (image 2). Using this approach, several centers found overall recurrence and survival rates identical to those obtained with hockey stick or large-field RT [30-34]. Clinicians who prescribe RT should tailor the RT fields by lowering the superior border from the top of T11 to the top of T12 and by ensuring the RT field is contoured to the ventricles to ensure the heart receives no direct RT. While these are lower than the usually recommended fields, it should be noted that the fields utilized historically were obtained in an era before CT was available for treatment planning. Additionally, support for these borders comes from a survey of 90 patients in which 97 percent of nodal metastases were localized to a smaller area than that which conventionally targeted RT fields encompass [35].
The MRC Testicular Tumor Working Group TE10 trial randomly assigned 478 males with stage I seminoma to paraaortic strip or paraaortic plus ipsilateral iliac lymph node RT following inguinal orchiectomy [36]. The short-term side effects of RT were decreased, and the incidence of azoospermia was significantly decreased using paraaortic strip RT compared with a more extensive RT field (11 versus 35 percent). With a median follow-up of 4.5 years, there were nine relapses in each group (4 percent). There was only one death due to seminoma in the trial.
Adjuvant mediastinal RT is not necessary to minimize the risk of relapse, and it leads to an unacceptably high long-term risk of cardiopulmonary disease [37].
Dose — Due to the radiosensitivity of seminoma, a low therapeutic dose is required to effectively treat seminoma, with a recommended dose of 20 Gy in 10 fractions [38,39]. A scrotal shield should be used, even with paraaortic strip radiation, to minimize radiation to the remaining testicle [40].
The effect of dose was studied in the MRC TE18 trial, in which 625 males with seminoma were randomly assigned to 20 Gy in 10 fractions or 30 Gy in 15 fractions [38]. With a median follow-up of five years, the disease-free survival rates were 98 and 97 percent for the 30 and 20 Gy groups, respectively [38]. While males receiving the higher dose had significantly more lethargy (20 versus 5 percent) and inability to work (46 versus 28 percent) at four weeks, these differences disappeared by 12 weeks. However, six new primary cancers were diagnosed, all in males treated with 30 Gy. Nine new germ cell primary cancers were diagnosed, six in the 20 Gy group, and three in the 30 Gy group.
Recurrent disease — Recurrent disease typically is detected by imaging studies. When a recurrence is limited to the retroperitoneal lymph nodes, this is typically treated like stage II seminoma. (See "Treatment of stage II seminoma".)
If more extensive disease is present, treatment is based on risk stratification. (See "Initial risk-stratified treatment for advanced testicular germ cell tumors".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Testicular cancer".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Testicular cancer (The Basics)")
●Beyond the Basics (see "Patient education: Testicular cancer (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Prognosis – The overall prognosis of patients with stage I testicular seminoma is excellent following orchiectomy. (See 'Introduction' above.)
●Surveillance – For patients with stage I testicular seminoma, we recommend surveillance rather than adjuvant treatment (algorithm 1) (Grade 1B). (See 'Surveillance' above.)
●Patients who are not candidates for surveillance
•Adjuvant carboplatin – For patients who decline surveillance, want to minimize any risk of relapse, and understand the risk of adverse late effects, we suggest adjuvant chemotherapy with single-agent carboplatin rather than radiation therapy (RT) (Grade 2C). While some UpToDate contributors prefer two cycles of carboplatin which is associated with a reduced risk of relapse, other contributors offer one cycle of carboplatin since overall survival (OS) outcomes are similar and the long-term toxicities of carboplatin are unknown. (See 'Adjuvant chemotherapy' above.)
•Adjuvant RT – Adjuvant RT is an appropriate alternative for patients who do not adhere to surveillance and who decline chemotherapy. (See 'Adjuvant radiation therapy' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Clair J Beard, MD, and William K Oh, MD, who contributed to earlier versions of this topic review.
